Short-term depression and long-term plasticity together tune sensitive range of synaptic plasticity

Abstract Synaptic efficacy is subjected to activity-dependent changes on short- and long time scales. While short-term changes decay over minutes, long-term modifications last from hours up to a lifetime and are thought to constitute the basis of learning and memory. Both plasticity mechanisms have been studied extensively but how their interaction shapes synaptic dynamics is little known. To investigate how both short- and long-term plasticity together control the induction of synaptic depression and potentiation, we used numerical simulations and mathematical analysis of a calcium-based model, where pre- and postsynaptic activity induces calcium transients driving synaptic long-term plasticity. We found that the model implementing known synaptic short-term dynamics in the calcium transients can be successfully fitted to long-term plasticity data obtained in visual- and somatosensory cortex. Interestingly, the impact of spike-timing and firing rate changes on plasticity occurs in the prevalent firing rate range, which is different in both cortical areas considered here. Our findings suggest that short- and long-term plasticity are together tuned to adapt plasticity to area-specific activity statistics such as firing rates. Author summary Synaptic long-term plasticity, the long-lasting change in efficacy of connections between neurons, is believed to underlie learning and memory. Synapses furthermore change their efficacy reversibly in an activity-dependent manner on the subsecond time scale, referred to as short-term plasticity. It is not known how both synaptic plasticity mechanisms – long- and short-term – interact during activity epochs. To address this question, we used a biologically-inspired plasticity model in which calcium drives changes in synaptic efficacy. We applied the model to plasticity data from visual- and somatosensory cortex and found that synaptic changes occur in very different firing rate ranges, which correspond to the prevalent firing rates in both structures. Our results suggest that short- and long-term plasticity act in a well concerted fashion.